JP4353801B2 - Process for producing 1- (pyrimidin-2-yl) propan-2-ones - Google Patents

Abstract

A process for the preparation of 1-(pyrimidin-2-yl)propan-2-ones of general formula (I), in which R is in each case a C<SUB>1-10</SUB>-alkyl group, a C<SUB>3-8</SUB>-cycloalkyl group, an alkyl group or an aryl-C<SUB>1-4</SUB>-alkyl group. For this, a malondiimidate of the general formula (II), in which R has the meaning given above, is reacted with diketene. The compounds which can be prepared according to the invention are intermediates for the synthesis of agrochemical active ingredients.

Description

  The present invention has the following general formula:

［式中、Ｒは、各々、Ｃ_1-10−アルキル基、Ｃ_3-8 −シクロアルキル基、アリル基またはアリール−Ｃ_1-4 −アルキル基である］
で表される１−（ピリミジン−２−イル）プロパン−２−オン類の製造方法に関する。ここで及び以降の記載において、Ｃ_1-10−アルキル基とは、１〜１０個の炭素原子を有する線状もしくは分枝状の第一、第二もしくは第三アルキル基の全てを意味するものと理解され、例えば、メチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、sec-ブチル、tert- ブチル、ペンチル、イソペンチル、tert- ペンチル、ネオペンチル、ヘキシル、ヘプチル、オクチル、ノニルまたはデシルである。Ｃ_3-8 −シクロアルキルとは、特に、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル及びシクロオクチルを意味するものと理解される。アリール−Ｃ_1-4 −アルキル基は、アリール基と１〜４個の炭素原子を有するアルキル基とから構成される基であり、この際、アリール基とは、特に、フェニル基またはナフチル基を意味するものと理解される。また、上記アリール基は、一つまたは二つ以上のＣ_1-4 −アルキル基、Ｃ_1-4 −アルコキシ基またはハロゲン原子によって置換されていてもよい。アリール−Ｃ_1-4 −アルキル基の例は、特に、ベンジル、１−フェニルエチル、２−フェニルエチル及び３−フェニルプロピルである。

[Wherein R is a C _1-10 -alkyl group, a C _3-8 -cycloalkyl group, an allyl group or an aryl-C _1-4 -alkyl group, respectively]
The manufacturing method of 1- (pyrimidin-2-yl) propan-2-one represented by these. Here and in the following description, a C _1-10 -alkyl group means any linear or branched primary, secondary or tertiary alkyl group having 1 to 10 carbon atoms. For example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl or decyl. C _3-8 -cycloalkyl is understood to mean in particular cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. The aryl-C _1-4 -alkyl group is a group composed of an aryl group and an alkyl group having 1 to 4 carbon atoms. In this case, the aryl group is particularly a phenyl group or a naphthyl group. Is understood to mean. The aryl group may be substituted with one or more C _1-4 -alkyl groups, C _1-4 -alkoxy groups or halogen atoms. Examples of aryl-C _1-4 -alkyl groups are in particular benzyl, 1-phenylethyl, 2-phenylethyl and 3-phenylpropyl.

  The compounds of the above formula I, in particular dimethoxy compounds (R = Me), can be used as intermediates in the synthesis of pesticidal active ingredients.

  The synthesis of these compounds has never been disclosed in the prior art.

  One of the objects of the present invention is to provide a production method that is simple and suitable for an industrial scale.

  According to the invention, this object is achieved by the method of claim 1. Easily available from malodinitrile and the corresponding alcohol (German Patent Application No. 2426913, European Patent Application Publication No. 0024200),

［式中、Ｒは上記の意味を有する］
で表されるマロンジイミデート類が、次式

[Wherein R has the above-mentioned meaning]
The maroon diimidates represented by

で表されるジケテンと直接反応し、所望の化合物（Ｉ）を良好な収率で生成することが見出された。

It has been found that the desired compound (I) is produced in good yields by reacting directly with the diketene represented by

  The malondiimidates (II) may be used without a diluent (as the free base) or may be generated from the corresponding salt and base in situ in the reaction. This base may be an inorganic base or an organic base such as a tertiary amine. The malondiimidates are preferably used without a diluent. For this purpose, malondiimidates are simply extracted from a neutralized solution of one of their salts, for example, with a low polarity solvent, such as dichloromethane or diethyl ether, and the solvent is evaporated. (European Patent Application Publication No. 0024200).

  The salt of malondiimidates (II) used is preferably dihydrochloride.

  The process of the present invention preferably uses 1- (4,6-dimethoxypyrimidin-2-yl) propan-2-one using dimethylmalondiimidate (R = Me) as malondiimidate (II). Used in the manufacture of

  The process of the invention is advantageously carried out in a solvent which is essentially inert under the reaction conditions, for example an aromatic hydrocarbon such as toluene or xylene, or a ketone such as acetone. The reaction temperature is preferably 50 to 150 ° C. when an aromatic solvent is used, and preferably 0 to 100 ° C. when a ketone solvent is used.

  The following examples illustrate how to perform the method of the present invention, but these examples are not intended to impose any limitation on the present invention.

Example 1
1- (4,6-Dimethoxypyrimidin-2-yl) propan-2-one A solution of dimethylmalondiimidate (80 g, 0.61 mol) in toluene (240 ml) was heated to 80 ° C. Diketene (103.44 g, 1.23 mmol) was added over 2 hours. At this time, the temperature was maintained at 80 ° C. The reaction mixture was maintained at 80 ° C. for an additional 2 hours and then cooled to room temperature. After adding water (200 ml), the mixture was stirred for 0.5 hours and separated. The aqueous phase was extracted with toluene (590 ml) and the combined organic phases were dried using sodium sulfate. Filtration followed by evaporation of the solvent under reduced pressure yielded 117.3 g of a reddish liquid crude product. The crude product was purified by distillation on a 20 cm Vigreux column.
Yield: 61.29 g, purity (GC)> 98% (55% of theory based on dimethylmalondiimidate).
B. p. : 90 ° C / 0.4mbar
¹ H-NMR (CDCl ₃ ): δ = 5.92 (s, 1H); 3.91 (s, 6H); 3.86 (s, 2H); 2.27 (s, 3H). In addition, the spectrum also has an enol-type signal.
Example 2
1- (4,6-dimethoxypyrimidin-2-yl) propan-2-one dimethylmalondiimidate dihydrochloride (90.0 kg, 443 mol, 1 eq) and acetone (330 L) in a 630 L volume under nitrogen atmosphere In a stirring vessel. The resulting suspension was cooled to 0-5 ° C. and triethylamine (98.7 kg, 975 mol, 2.2 eq) was added over 120 minutes at a temperature of 0-5 ° C. The suspension was stirred at 0-5 ° C for an additional 30 minutes and then warmed to 25 ° C. Diketene (44.7 kg, 531 mol, 1.2 eq) was added at about 25 ° C. within 90 minutes. After the addition was complete, the resulting mixture was heated to 30 ° C. and after a reaction time of 2 hours at the same temperature, excess methanol was added by adding methanol (15 L) and 4- (dimethylamino) pyridine (0.5 kg). Diketene was decomposed. The precipitated triethylammonium chloride (about 160 kg) was filtered off and the filter cake was washed with acetone (2 × 113 L). The combined filtrates were concentrated by distilling off acetone (450-500 L) under ambient pressure. The remaining solution was cooled to 40 ° C. and water (198 L) was added. In order to completely remove the acetone, the solution is subjected to further distillation steps under 100-200 mbar until the top temperature is about 45 ° C. (after about 5 hours) and about 150-180 L of distillate is obtained. It was attached. The residue was cooled to 30 ° C., seeded with 1- (4,6-dimethoxypyrimidin-2-yl) propan-2-one crystals (0.6 kg) and then cooled to 0 ° C. within 60 minutes. . After an additional 60 minutes at 0 ° C., the product was filtered, washed with cold water (135 L) and dried at 35 ° C./<100 mbar (16 h).
Yield: 49 kg (55%), slightly yellowish solid, purity> 95%.

Claims (5)

The following general formula

[Wherein R is a C _1-10 -alkyl group, a C _3-8 -cycloalkyl group, an allyl group or an aryl-C _1-4 -alkyl group, respectively]
A process for producing 1- (pyrimidin-2-yl) propan-2-ones represented by the following general formula:

[Wherein R has the above-mentioned meaning]
The following formula

The method described above, which comprises reacting with a diketene represented by the formula: Process according to claim 1, characterized in that malondiimidate (II) is generated in situ from the corresponding salt and base. Process according to claim 2, characterized in that the salt of malondiimidate (II) used is the dihydrochloride salt. 4. A process according to claim 2 or 3, characterized in that the base is a tertiary amine. 5. The process as claimed in claim 1, wherein the malondiimidate (II) used is dimethylmalondiimidate.